ABSTRACT This proposal is to request support for a pair of concurrent 2008 Keystone Symposia meetings entitled "NK and NKT Cell Biology" (organized by Michael B. Brenner and Lewis L. Lanier), and "Innate Immunity: Signaling Mechanisms" (organized by Luke A.J. O'Neill, J[unreadable]rg Tschopp and Shizuo Akira), which will be held in Keystone, Colorado from February 24 - 29, 2008. NK cells and NKT cells play a central role in orchestrating and amplifying the innate response - and in shaping the nature of the adaptive response of T cells and B cells. The NK and NKT Cell Biology meeting will bring together, for the first time, researchers focusing on NK cells and NKT cells. This should initiate discussions, foster collaborations and lead to a better understanding how these cells use independent recognition mechanisms to achieve common effector functions and work coordinately to mediate immune responses against tumors and pathogens, as well as influence autoimmunity. With regard to the meeting on Innate Immunity: Signaling Mechanisms, the past 5 years has seen remarkable progress in our understanding of the molecular basis for innate immunity. New families of receptors have been discovered that sense microbial products, including Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors. In addition, signaling mechanisms activated by these receptor families have been described, with new adapter proteins, protein kinases and transcription factors being found. Breakthroughs in our understanding of signaling mechanisms is a key aspect for this field, with much excitement and insight being generated. This Keystone Symposia meeting will assemble the world's leading investigators in cell signaling during innate immunity, to present recent data and discuss the importance of signaling in the more general context of innate immunity. We can expect a compelling and informative meeting that will bring together basic researchers in the area but also those more generally interested in leading edge research in innate immunity. The pairing of these two Keystone Symposia meetings will stimulate productive interactions between experts in the areas of NK/NKT biology and innate immunity.